Liposome-Mediated Inhibition of Inflammation by Hydroxycitrate.

Hydroxycitrate (HCA), a main organic acid component of the fruit rind of , is a natural citrate analog that can inhibit the ATP citrate lyase (ACLY) enzyme with a consequent reduction of inflammatory mediators (i.e., nitric oxide (NO), reactive oxygen species (ROS), and prostaglandin E (PGE)) levels. Therefore, HCA has been proposed as a novel means to prevent, treat, and ameliorate conditions involving inflammation. However, HCA presents a low membrane permeability, and a large quantity is required to have a biological effect. To overcome this problem, HCA was formulated in liposomes in this work, and the enhancement of HCA cell availability along with the reduction in the amount required to downregulate NO, ROS, and PGE in macrophages were assessed. The liposomes were small in size (~60 nm), monodispersed, negatively charged (-50 mV), and stable on storage. The in vitro results showed that the liposomal encapsulation increased by approximately 4 times the intracellular accumulation of HCA in macrophages, and reduced by 10 times the amount of HCA required to abolish LPS-induced NO, ROS, and PGE increase. This suggests that liposomal HCA can be exploited to target the citrate pathway involved in inflammatory processes.